2005/12/13

Scythe Balances Life And Death During Development

Scythe Balances Life And Death During Development: "A protein called Scythe determines which cells live and which die during the growth and development of the mammalian embryo.

Scythe plays a critical role during development of mammals by selectively regulating when and where specific cells either proliferate or undergo apoptosis, the process by which cells self-destruct. Understanding exactly how Scythe balances apoptosis with cell proliferation could provide significant insights into how organs develop in the growing embryo.

Previous work by other researchers suggests that the Scythe protein might work by regulating the folding and activity of the molecules that make up the signaling pathway that controls apoptosis. Scythe was also known to interact with another protein called Reaper to control development of the fruit fly. Therefore, the St. Jude team developed laboratory models lacking both copies of Scythe to study what happens in the gene's absence. The scientists discovered that major defects in lung development appeared late in the process of embryo development.

Cells from the Scythe-/- model responded to ionizing radiation and hydrogen peroxide by undergoing apoptosis like normal cells. However, these cells were more resistant to menadiaone and thapsigarin--two chemicals known to trigger apoptosis. But when the investigators put Scythe genes back into the cells, they became sensitive to these treatments and underwent apoptosis.

"These chemicals affect the movement of calcium inside a special structure where proteins are made," McKinnon said. "This showed that Scythe helps trigger apoptosis in specific circumstances. Further studies are currently underway to elucidate this process."
Part of the Scythe molecule resembles that of molecules known to be involved with protein destruction, according to Fabienne Desmots, the postdoctoral researcher in the Department of Genetics and Tumor Cell Biology who did much of the work on this project. This finding suggests that Scythe might help to regulate the signaling molecules that are involved in either apoptosis or cell proliferation."

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